Not Applicable
This invention relates to methods and devices for improved collection and focusing of ions generated at or near atmospheric pressure for introduction into the mass spectrometer, ion mobility or ion and charged particle or droplet deposition onto surfaces.
The generation of ions at atmospheric pressure is accomplished by a variety of means; including, electrospray (ES), atmospheric pressure chemical ionization (APCI), atmospheric pressure matrix assisted laser desorption ionization (MALDI), discharge ionization, 63Ni sources, inductively coupled plasma ionization, and photoionization. A general characteristic of all these atmospheric sources is the dispersive nature of the ions once produced. Needle sources such as electrospray and APCI disperse ions radially from the axis in high electric fields emanating from needle tips. Aerosol techniques disperse ions in the radial flow of gases emanating from tubes and nebulizers. Even desorption techniques such as atmospheric pressure MALDI will disperse ions in a solid angle from a surface. The radial cross-section of many dispersive sources can be as large as 5 or 10 centimeters in diameter. As a consequence of a wide variety of dispersive processes, efficient sampling of ions from atmospheric pressure sources to small cross-sectional targets or through small cross-sectional apertures and tubes (usually less than 1 mm) into a mass spectrometer becomes quite problematic. This is particularly amplified if the source on ions is removed from the regions directly adjacent to the aperture.
The simplest approach to sampling dispersive atmospheric sources is to position the source on axis with a sampling aperture or tube. The sampling efficiency of simple plate apertures is generally less than 1 ion in 104. Devices developed by Fite (U.S. Pat. No. 4,209,696) used pinhole apertures in plates with electrospray. Devices developed by Laiko and Burlingame (W.O. Pat. No. 99/63576 and U.S. Pat. No. 5,965,884) used aperture plates with atmospheric pressure MALDI. An atmospheric pressure source by Kazuaki et al (Japan Pat. No. 04215329) is also representative of this inefficient approach. This general approach in severely restricted by the need for precise aperture alignment and source positioning and very poor sampling efficiency.
A wide variety of source configurations utilize conical skimmer apertures in order to improve collection efficiency over planar devices. This approach to focusing ions from atmospheric sources is limited by the acceptance angle of the field generated at the cone. Generally, source position relative to the cone is also critical to performance, although somewhat better than planar apertures. Conical apertures are the primary inlet geometry for commercial ICP/MS with closely coupled and axially aligned torches. Examples of conical-shaped apertures are prevalent in ES and APCI (U.S. Pat. No. 5,756,994), and ICP (U.S. Pat. No. 4,999,492) inlets. As with planar apertures, source positioning relative to the aperture is critical to performance and collection efficiency is quite low.
One focusing alternative utilizes a plate lens with a large hole in front of an aperture plate or tube for transferring sample into the vacuum system. The aperture plate is generally held at a high potential difference relative to the plate lens. The configuration creates a potential well that penetrates into the source region and has a significant improvement in collection efficiency relative to the plate or cone apertures. This configuration has a clear disadvantage in that the potential well resulting from the field penetration is not independent of ion source position, or potential. High voltage needles can diminish this well. Off-axis sources can affect the shape and collection efficiency of the well. Optimal positions are highly dependent upon both flow (gas and liquid) and voltages. They are reasonable well suited for small volume sources such as nanospray. Larger flow sources become less efficient and problematic. Because this geometry is generally preferential over plates and cones, it is seen in most types of atmospheric source designs. We will call this approach the xe2x80x9cPlate-wellxe2x80x9d design which is reported with apertures by Labowsky et al. (U.S. Pat. No. 4,531,056), Covey et al. (U.S. Pat. No. 5,412,209) and Franzen (U.S. Pat. No. 5,747,799). There are also many Plate-well designs with tubes reported by Fenn et al. (U.S. Pat. No. 4,542,293), Goodley et al. (U.S. Pat. No. 5,559,326), and Whitehouse et al. (U.S. Pat. No. 6,060,705). 
Several embodiments of atmospheric pressure sources have incorporated grids in order to control the sampling. Jarrell and Tomany (U.S. Pat. No. 5,436,446) utililized a grid that reflected lower mass ions into a collection cone and passed large particles through the grid. This modulated system was intended to allow grounded needles and float the grid at high alternating potentials. This device had limitations with duty cycle of ion collection in a modulating field (non-continuous sample introduction) and spatial and positioning restrictions relative to the sampling aperture. Andrien et al (U.S. Pat. No. 6,207,954 B1) used grids as counter electrodes for multiple corona discharge sources configured in geometries and at potentials to generated ions of opposite charge and monitor their interactions and reactions. This specialized reaction source was not configured with high field ratios across the grids and was not intended for high transmission and collection, rather for generation of very specific reactant ions. An alternative atmospheric pressure device by Yoshiaki (Japan Pat. No. 10088798) utilized hemispherical grids in the second stage of pressure reduction. Although the approach is similar to the present device in concept, it is severely limited by gas discharge that may occur at low pressures if higher voltages are applied to the electrodes and most of the ions are lost at the cone-aperture from atmospheric pressure into the first pumping stage.
Grids are also commonly utilized for sampling ions from atmospheric ion sources utilized in ion mobility spectrometry (IMS). Generally, for IMS analysis ions are pulsed through grids down a drift tube to a detector as shown in Kunz (U.S. Pat. No. 6,239,428B1). Great effort is made to create planar plug of ions in order to maximize resolution of components in the mobility spectrum. These devices generally are not continuous, nor do they require focusing at extremely high compression ratios.
A preferred embodiment of the invention is the configuration of a Laminated High Transmission Element (L-HTE) (as shown in FIG. 5A), comprising an electrical insulating base, and a layer of conducting meshed-surfaces laminated on both sides. The L-HTE is configured downstream from any of a variety of atmospheric pressure sources and upstream from an Inner Field-Shaping Electrode and a conducting collector surface (aperture plate or tube). Ions generated in a relatively large volumetric area of an atmospheric pressure source are attracted toward the top surface of the L-HTE by an attracting potential relative to the source region.
The field ratio, the field strength on the source side of the high transmission element relative to the collector side is maintained at a lower value (generally 1-10xc3x97 less) than the field strength equidistant to the collector side of the L-HTE. In this operating condition, the field from the collector side of the L-HTE penetrates into the source side of the L-HTE and accelerates appreciably all of the ions through the openings in the L-HTE surface. Typically, the field ratio value is calculated at a distance of several opening diameters away from the surface. A good value of a field ratio is greater than 10.
The L-HTE is typically manufactured so to allow ions to pass easily through the L-HTE surface. This entails having a L-HTE with a low depth aspect ratio, referring to the ratio of the dimension of the openings to the thickness of the L-HTE surface; where the thickness of the insulating base and metal laminates are as thin as mechanically possible. In addition, the openness of the L-HTE is also important. Typically the openness, the ratio of the dimension of the opening to the entire surface area should be as large as possible to allow the field from the metal laminated on the collector side to penetrate through the metal laminated on the source side of the L-HTE and into the source side several opening diameters away from the source side surface of L-HTE.
The focusing side metal laminate of the L-HTE and the inner field-shaping electrode are held at approximately the same potential relative to the collector surface which is held at extremely high potential difference to attract virtually all ions that cross the L-HTE, through a relatively large aperture in the inner field-shaping electrode, onto the collector surface (or through an aperture into the vacuum). The combination of L-HTE shape, Inner Field-shaping Electrode aperture size, and potential difference (between the HTE and the collector) affect substantial compression of the dispersed ions into a small cross-sectional beam at the collector. When this beam is precisely aligned with a vacuum sampling aperture into a mass spectrometer, very high sensitivities are achieved.
The physical separation of the ionization source region from the deep potential-well focusing region by the L-HTE solves many of the efficiency problems associated with conventional approaches to ion collection at atmospheric pressure. With the present invention, dispersed ions are not required to be focused to a small diameter in the ion source region, rather, they are required to drift toward a relatively large front surface of the L-HTE. In this way all ions from a given source can be collected across an appropriately sized and shaped L-HTE surface, then focused in the high field of the focusing well.
One object of the present invention is to increase the collection efficiency of ions and/or charged particles at a collector, or through an aperture or tube into a vacuum system, by creating a very small cross-sectional area beam of ions and/or charged particles from highly dispersed atmospheric pressure ion sources. Another object of the present invention is to increase the transmission efficiency of ions from atmospheric pressure ion sources to a target collector, or through an aperture or tube. The present invention has a significant advantage over prior art in that the use of a Laminated High Transmission Element (L-HTE) to separate the regions of ion generation from ion focusing allows precise shaping of fields in both regions. Ions can be generated in large ion source regions without losses to walls. Droplets have longer time to evaporate and/or desorb ions without loss from the sampling stream. Source temperatures can be lower because rapid evaporation is not required. This can prevent thermal decomposition of some labile compounds. Counter electrodes for electrospray needles do not have to be the plate lens as practices with most convention sources or even the L-HTE. The aerosol can be generated remotely and ions can be allowed to drift toward the L-HTE.
Another object of the present invention is to have collection efficiency be independent of ion source position relative to the collection well. With the present invention there is no need for precise mechanical needle alignment or positioning relative to collectors, apertures, or tubes invention. Ions generated at any position in the ion source region are transmitted to the collector, aperture, or tube with similar efficiency. No existing technology has positional and potential independence of the source. The precise and constant geometry, and alignment of the focusing well with sampling apertures will not change with needle placement. The fields inside (focusing side) the well will not change, even if they change outside (source side).
Another object of the present invention is the independence of ion source type. This device is capable of transmission and collection of ions from any atmospheric (or near atmospheric) source; including, electrospray, atmospheric pressure chemical ionization, atmospheric pressure MALDI (laser desorption), inductively coupled plasma, discharge sources, 63Ni sources, spray ionization sources, induction ionization sources and photoionization sources. The device is also capable of sampling ions of only one polarity at a time, but with extremely high efficiency.
Another object of the present invention is to efficiently collect and/or divert a flow of ions from more than one source. This can be performed in a simultaneous fashion for introduction of mass calibrants from a separate source and analytes from a different source at a different potential; conversely, it can be performed sequentially as is typical with multiplexing of multiple chromatographic streams introduced into one mass spectrometer.
Another object of the present invention is to efficiently transmit ions to more than one target position. This would have the utility of allowing part of the sample to be collected on a surface while another part of the sample is being introduced through an aperture into a mass spectrometer to be analyzed.
Another object of the present invention is to improve the efficiency of multiplexed inlets from both multiple macroscopic sources and micro-chip arrays, particularly those developed with multiple needle arrays for electrospray. Position independence of this invention make it compatible with a wide variety of needle array technologies and multi-well plates for surface desorption techniques.
Another object of the present invention is to remove larger droplets and particles from aerosol sources with a counter-flow of gas to prevent contamination of apertures, tubes, and vacuum components.
Another object of the present invention is to collect all the ions or charged particles or droplets at the outer surface (upstream side) of the L-HTE but to also be able to selectively and spatially sample a select group of ions through the surface. Allowing the efficient application (deposition) of charged compounds on a surface in patterns determined by the shape of the L-HTE, whether the opening permits the transfer of the charged compounds, or by the shape and size of the openings.
Another objective of the present invention is that the precise alignment of the individual openings of the L-HTE with a combination of electrostatic potentials and gas flows, both concurrent and countercurrent, substantially all of the charged compounds can be transferred through the surface.
An advantage of the present device is the independence of collection efficiency of a source of ions from the sampling efficiency of the ions into a gas-phase ion analyzer. Multiple sources are able to be uniformly collected with this invention. Multiple focal points can also be configured if there is need to collect part of the sample and analyze another part.
An additional advantage of the present device is that the addition of gas flow, concurrent and countercurrent to the motion of the ions, provides additional focusing to the ions passing through the L-HTE. As the ions move through the L-HTE a countercurrent flow of gas focuses the ions toward the center of the openings, away from surfaces, and as the ions exit the openings a concurrent flow of gas prevents their radial dispersion focusing the ions axially; whereby the electrostatic direct current potential ratio across the L-HTE can be less than 1.